Matt Johnson David Dewar

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COELIAC DISEASE

• Matt Johnson David Dewar
• Professor Paul Ciclitira
• St Thomas Hospital, London

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Mortality

• Almost all mortality in CD is due to malignancy
• gt50 due to EATCL
• Other tumours mouth, oesophagus, sb
• Mortality 1.9-3.4x control population
• Holmes et al 2x control pop1
• Mortality normal after 5 yrs on GFD2

1Holmes GK et al (1976) Gut 17(8) 612-9 2Holmes
GK et al (1989) Gut 30(3) 333-8
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Prevalence of coeliac disease

• Sweden 167 antibody positive
• Ireland 1100
• England 1150
• Europe 1300
• N America 1300
• Australia 1300

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Cereal Taxonomy

• Family GRAMINEAE
• Subfamily FESUCOIDEAE
  PANICOIDEAE
• Tribe TRITICEAE
  AVENEAE ORYZEAE TRIPSACEAE
• Subtribe TRITICINAE
• Genus TRITICUM SECALE HORDEUM AVENA
  ORYZA ZEA
• Species WHEAT RYE BARLEY
  OATS RICE MAIZE

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Are oats safe in coeliac disease?

• Pure oat products are probably safe
• Janatuinen et al 2002 Gut. (Finland)
• 5 year follow up of oat and non-oat eating
  coeliacs
• No clinical, serological and histological
  differences at 5 years.
• UK oat products may have contamination
  (harvesting, milling, food preparation)
• Gluten free Food industry standards 200 ppm

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Tissue transglutaminase

• Auto-antigen target of anti-endomyseal antibodies
• Intracellular, released during inflammation
• Cross links matrix proteins, stabilising
  connective tissue during inflammation.
• Deamidates specific glutamine residues.
• Creation of neo-epitopes with gluten

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TAKE THAT VILLUSES
GLUTEN
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Pathology the coeliac lesion

• Villus atrophy
• Crypt hyperplasia
• Loss of enterocyte height
• Lamina propria infiltration
• Increased intra-epithelial lymphocytes
• Increased mitotic activity

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Intra-epithelial lymphocytes
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NORMAL SMALL INTESTINE
COELIAC DISEASE
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Clinical categories of coeliacs

• Coeliac disease
• Undiagnosed coeliac disease
• Silent coeliac disease
• Latent coeliac disease

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Clinical features in adults

• Lethargy Tired all the time
• Anaemia (Fe, folate, B12 and mixed)
• Abdominal pain
• Non-specific abdominal symptoms
• Diarrhoea
• Weight loss
• Osteoporosis
• Sub-fertility

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Associations

• Dermatitis herpetiformis
• IgA deficiency
• SBBO
• Hyposplenism
• Autoimmune conditions
• Thyroid disease
• Type 1 diabetes
• Addisons
• Sjogrens syndrome

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AD and age at diagnosis

• Group Prevalence AD
• A1 agelt2yrs 5.1
• A2 age 2-10yrs 17
• A3 agegt10yrs 23.6
• Prevalence of autoimmune disease is related to
  duration of gluten exposure

Ventura A (1999) Gastroenterology 117297-303
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Osteoporosis

• 47 women lt 50 men on GFD have osteopenia /
  osteoporosisa
• Improvement 1 year post treatmentb

aMcFarlane (1995) Gut 36710-14 bValdimarsson
(1996) Gut 38322-7
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DERMATITIS HERPETIFORMIS
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Dermatitis Herpetiformis

• 2 -3
• IgA deposition at the basement membrane
• Rx
• 1) GFD 6-12/12
• 2) Dapsone

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SBBO

• 8 of non-responsive coeliac patients
• Symptoms
• Diarrhoea gt Pain gt Weight loss gt Bloating gt
  Flatulence gt Nausea gt Steatorrhoea
• Nutritional deficiencies
• Vit D (tetany) gt Vit A (night blindness) gt
  Cobalamin (neuropathy) gt Vit B12 (macrocytosis)
• Ix H2 Lactose / Glucose breath test
• Rx 7-10/7 course of
• Co-amoxiclav Metronidazole
• Cephalexin Co-trimoxazole
• Gentamicin Metronidazole

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Hyposplenism

• ? 80 of coeliac patients have evidence of
  hyposplenism Vasquez 1991
• Features
• Howell Jolly bodies, target cells,
  thrombocytopenia
• Mx
• Meningococcal, Pneumococcal HIB vaccinations
• Prophylactic antibiotics

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Microscopic colitis (5)

• The Cochrane database 5 RCTs
• 3 x Budesonide 9mg od tapering over 8/52
• significant symptomatic and histological benefit
• anecdotal evidence suggesting long term
  remission.
• 1 x Bismuth subsalicylate (n12), three chewable
  262mg tablets tds for 8/52
• symptomatic and histological improvement
• with resolution of the collagenous band
• Pepto-Bismol has three different potential modes
  of action as an antibacterial, anti-inflammatory
  and anti-diarrhoeal
• Denol does not have the subsalicylate component
• 1 x High dose Prednisolone (50mg)
• can provide symptom relief, but often without
  histological improvement
• relapses are common
• Given the evidence, we advocate using
• 1st and 2nd line therapy Budesonide and
  bismuth subsalicylate (Pept-Bismol)
• 3rd line consider trying mesalazine in LC and
  cholestyramine in CC

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Ulcerative jejunitis

• Rare (6th decade)
• Related to Enteropathy-associated T cell lymphoma
  (EATL)
• Gastroscopy / Enteroscopy - May be segmental
• Laparoscopy and full thickness biopsy
• CT / repeat barium studies
• T Cell receptor PCR monoclonality
• UCL Prof. Isaacson
• Atypical gTcell receptor abnormalities
• Steroids, nutritional support, close observation

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MRI
CT
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Diagnosis

• Serology
• D2 Bx (3 biopsies with jumbo forceps)
• Repeat biopsy on gluten-free diet
• Repeat challenge (gt10g per day, 2/52)
• ESPGAN guidelines

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Coeliac antibodies

• Anti-reticulin, anti-gliadin, anti-jejunal
• Anti-endomysial
• Anti-tissue transglutaminase

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Serological screening tests
Sensitivity Specificity
IgA Anti-Gliadin 83 82
IgA Anti Endomysium 90 99
IgA Anti tissue transglutaminase (Human Umbilical cord) 93 95
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Developments in serological tests

• IgA deficiency occurs in 2-3 of coeliacs
• Coeliacs disease occurs in 8 of IgA deficients
• Serology Ix
• IgG1 subgroup testing more specific than IgG
• Combine both IgA and IgG1 EMA/tTG testing
• 10-15 are symptomatic
• Recurrent sinopulmonary infections
• AI associations
• Anaphylactic Transfusion Reactions
• GI Disorders (failure to clear large proteins
  from GI mucosal barrier

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Using Serology to Monitor Patients

• IgA gliadin and TTG normalise on a strict GFD
  after 3-6/12
• Must have pre-treatment levels
• IgG gliadin can be used but takes longer to
  normalise
• IgA endomyseal is costly and more difficult to
  quantify

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Screening Relatives Fraser J GUT 2004

• 1st Degree relatives 5-15
• 2nd Degree relatives no increased prevalence
• 11.4 of these would be missed using IgA EMA in
  isolation and so an algorithm has been devised
• Coeliac disease can occur in antibody negative
  individuals and that biopsy is recommended if
  there is a high index of suspicion.

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Algorithm for Screening 1? Relatives
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Treatment of coeliac disease

• Gluten-free diet
• Avoidance of wheat, rye and barley
• Oats (probably OK)
• Dietician
• Codex Alimentarius
• Coeliac societies handbook

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Treatment of coeliac disease

• Gluten-free diet
• Avoidance of wheat, rye and barley
• Oats (probably OK)
• Dietician
• Codex Alimentarius
• Coeliac societies handbook
• BUT NOT CORNFLAKES

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Efficacy of Gluten-free diet

• 70 respond symptomatically
• 30 refractory
• non-compliant
• inadvertent intake
• another diagnosis

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Dewar D, Johnson MW, Ciclitira PJ, GUT 2005
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Gluten-free diet failure

• Check diagnosis correct
• Consider second diagnosis
• pancreatic insufficiency
• Check Compliance
• inadvertent/intentional
• Refractory sprue
• REPEAT DUODENAL BIOPSY

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Pitfalls

• Insufficient advice (or effort)
• Malted cereals Cornflakes
• Beer contamination
• Cooking sauces
• Oat contamination

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Refractory coeliac disease

• Continued symptoms
• Prednisolone 7.5-20 mg
• Consider an immuno-modulator (AZA)
• Unwell
• Weight loss
• Hypoalbuminaemia
• Dehydration
• Steatorrhoea
• Prednisolone 0.5 mg/kg

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CD in the Elderly (5-20) Johnson,MW GUT 2003

• gt65yrs lt65yrs Stata p values
• Overall D2 Bx rate 276/628 (43.9) 222/576
  (38.8) 0.07
• Anaemia 223/351 (63.5) 96/118
  (81.4) 0.0003
• Malabsorption 27/30 (90) 77/79 (97.5) NS
• Atypical Dyspepsia 16/113 (14.2) 38/204
  (18.6) NS
• Abdominal pain 11/122 (9.8) 38/204
  (38) 0.03
• Altered Bowel habit 10/11 (90.9) 12/16
  (75) NS
• Weight loss 18/64 (28.1) 22/36
  (61.1) 0.0012
• Profound Tiredness 1/2 (50) 0/0 NA
• No. with combinations 3/57 (5.3) 3/71(4.2) NS
• No. diagnosed 4/628 (0.64) 17/576 (2.95)
  0.0001.
• Mortality 1/276 (3.6 per 1000) 0/222 0.0038

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Coeliac disease guidelines

• AGA Technical Review on Celiac Sprue
  Gastroenterology 2001 1201526-1540
• British Society of Gastroenterology 1996
• Guidelines for the Management of Patients with
  Coeliac Disease
• (soon to be updated)